Global Patent Index - EP 3210964 A1

EP 3210964 A1 20170830 - POSITIVELY CHARGED WATER-SOLUBLE PRODRUGS OF IBUPROFEN WITH VERY FAST SKIN PENETRATION RATE

Title (en)

POSITIVELY CHARGED WATER-SOLUBLE PRODRUGS OF IBUPROFEN WITH VERY FAST SKIN PENETRATION RATE

Title (de)

POSITIVGELADENE, WASSERLÖSLICHE PRODRUGS VON IBUPROFEN MIT EINER SEHR SCHNELLEN HAUTPENETRATIONSRATE

Title (fr)

PRO-MÉDICAMENTS D'IBUPROFÈNE HYDROSOLUBLES POSITIVEMENT CHARGÉS À TAUX DE PÉNÉTRATION CUTANÉE TRÈS RAPIDE

Publication

EP 3210964 A1 20170830 (EN)

Application

EP 17152505 A 20060718

Priority

  • EP 17152505 A 20060718
  • EP 06780126 A 20060718
  • IB 2006052461 W 20060718

Abstract (en)

Pro-drugs of ibuprofen comprising a thiopropionate or propionamide moiety, wherein the amino group is tertiary and protonated. This positively charged amino groups of these pro-drugs not only largely increases the solubility of the drugs, but also bonds to the negative charge on the phosphate head group of membranes and pushes the pro-drug into the cytosol. Diethylaminoethyl 2-(p-isobutylphenyl) propionate.AcOH for example diffuses through human skin 250 times faster than ibuprofen itself and 125 times faster than ethyl 2-(p-isobutylphenyl) propionate. In plasma, more than 90% of these pro-drugs can change back to the drug in a few minutes. The prodrugs can be used medicinally in treating any ibuprofen-treatable conditions in humans or animals and be administered not only orally, but also transdermally for any kind of medical treatments and avoid most of the side effects of ibuprofen, most notably GI disturbances such as dyspepsia, gastroduodenal bleeding, gastric ulcerations, and gastritis. Controlled transdermal administration systems of the prodrug enables the ibuprofen to reach constantly optimal therapeutic blood levels to increase effectiveness and reduce the side effects of ibuprofen.

IPC 8 full level

A61K 31/216 (2006.01); A61P 29/00 (2006.01); A61P 43/00 (2006.01); C07C 211/63 (2006.01); C07C 233/40 (2006.01); C07C 327/30 (2006.01)

CPC (source: EP)

A61P 11/06 (2017.12); A61P 15/00 (2017.12); A61P 17/00 (2017.12); A61P 17/10 (2017.12); A61P 19/02 (2017.12); A61P 25/04 (2017.12); A61P 25/06 (2017.12); A61P 27/02 (2017.12); A61P 27/06 (2017.12); A61P 27/14 (2017.12); A61P 27/16 (2017.12); A61P 29/00 (2017.12); A61P 35/00 (2017.12); A61P 43/00 (2017.12); C07C 211/63 (2013.01); C07C 233/40 (2013.01); C07C 327/30 (2013.01)

Citation (applicant)

Citation (search report)

  • [A] EP 0289262 A2 19881102 - SYNTEX PHARMA INT [BM]
  • [A] EP 0237495 A2 19870916 - SIGMA TAU IND FARMACEUTI [IT]
  • [A] US 2004022837 A1 20040205 - HSU TSUNG-MIN [US], et al
  • [A] WO 02085297 A2 20021031 - EPIGENESIS PHARMACEUTICALS INC [US], et al
  • [A] SHANBHAG, VRINDA R. ET AL: "Ester and amide prodrugs of ibuprofen and naproxen: synthesis, anti-inflammatory activity, and gastrointestinal toxicity", JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 81, no. 2, 1992, pages 149 - 154, XP000248778, ISSN: 0022-3549
  • [A] VENUTI M C ET AL: "SYNTHESIS AND BIOLOGICAL EVALUATION OF OMEGA-(N,N,N-TRIALKYLAMMONIUM) ALKYL ESTERS AND THIOESTERS OF CARBOXYLIC ACID NONSTEROIDAL ANTIINFLAMMATORY AGENTS", PHARMACEUTICAL RESEARCH, vol. 6, no. 10, 1 January 1989 (1989-01-01), KLUWER ACADEMIC PUBLISHERS, NEW YORK, NY, US, pages 867 - 873, XP001098334, ISSN: 0724-8741, DOI: 10.1023/A:1015960522189
  • [A] DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 2002, SONG, NI ET AL: "Synthesis of a quaternary ammonium derivative of ibuprofen", XP002590079, retrieved from STN Database accession no. 2003:29322 & SONG N ET AL: "Synthesis of a derivative quaternary ammonium-ibuprofen", JOURNAL OF OCEAN UNIVERSITY OF QINGDAO,, vol. 32, no. 6, 1 January 2002 (2002-01-01), pages 911 - 913, XP001539131, ISSN: 1001-1862
  • [A] FUNT ET AL: "Oral ibuprofen and minocycline for the treatment of resistant acne vulgaris", JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, C.V. MOSBY, ST. LOUIS, MO, US LNKD- DOI:10.1016/S0190-9622(85)80375-3, vol. 13, no. 3, 1 September 1985 (1985-09-01), pages 524 - 525, XP025590312, ISSN: 0190-9622, [retrieved on 19850901]
  • [A] TJEBBES G W A ET AL: "d-Ibuprofen in ocular inflammation induced by paracentesis of the rabbit eye", PROSTAGLANDINS, vol. 40, no. 1, 1 July 1990 (1990-07-01), BUTTERWORTH, STONEHAM, MA, US, pages 29 - 33, XP023448748, ISSN: 0090-6980, [retrieved on 19900701]
  • [A] W.F. DIVEN ET AL: "Treatment of experimental acute otitis media with ibuprofen and ampicillin", INT.J.PEDIATR.OTORHINOLARYNGOL., vol. 33, 1995, pages 127 - 139, XP002590081

Designated contracting state (EPC)

AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR

DOCDB simple family (publication)

WO 2008010025 A1 20080124; AU 2006346288 A1 20080124; CA 2657636 A1 20080124; CA 2657636 C 20211109; CN 101489985 A 20090722; CN 101489985 B 20140108; DK 2041068 T3 20170227; EP 2041068 A1 20090401; EP 2041068 A4 20100929; EP 2041068 B1 20170125; EP 3210964 A1 20170830; ES 2616315 T3 20170612; HK 1135958 A1 20100618; HU E033687 T2 20171228; JP 2009543857 A 20091210; JP 5144658 B2 20130213; PL 2041068 T3 20170531; PT 2041068 T 20170217

DOCDB simple family (application)

IB 2006052461 W 20060718; AU 2006346288 A 20060718; CA 2657636 A 20060718; CN 200680055379 A 20060718; DK 06780126 T 20060718; EP 06780126 A 20060718; EP 17152505 A 20060718; ES 06780126 T 20060718; HK 10100235 A 20100111; HU E06780126 A 20060718; JP 2009520065 A 20060718; PL 06780126 T 20060718; PT 06780126 T 20060718